Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.
Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.
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DOI：
10.1089/ars.2006.8.229
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发表时间：
2006-02
影响因子：
6.6
通讯作者：
Yan Wang;S. Feinstein;Y. Manevich;Y. Ho;A. Fisher
中科院分区：
文献类型：
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作者：
Yan Wang;S. Feinstein;Y. Manevich;Y. Ho;A. Fisher
最近描述的抗氧化酶过氧化物氧还蛋白6（Prdx 6）基因敲除的小鼠，评估了百草枯（PQ）给药对肺损伤的敏感性。对于高剂量PQ（30 mg/kg i. p.），所有Prdx 6-/-小鼠在4天时死亡（LT 50 54 +/-2.05小时，平均值+/- SE），而86%的野生型（WT）小鼠（C57 BL/6）存活（n = 14）。在PQ后2天，肺湿/干重比在Prdx 6-/-小鼠中显著增加（p < 0.05）至7.57 +/- 0.37，而在WT小鼠中为5.42 +/- 0.25。在Prdx 6-/-小鼠中，支气管肺泡灌洗液中的总蛋白和有核细胞以及肺匀浆中的TBARS和蛋白质羰基也显示出更显著的增加。PQ后2.5天，WT肺的光学显微镜检查显示轻度损伤，而Prdx 6-/-肺显示上皮细胞坏死、血管周围水肿和炎性细胞。与WT小鼠相比，使用低剂量PQ（12.5 mg/kg）时，死亡率和肺损伤不太明显，但使用Prdx 6-/-时显著更高。这些结果表明，使用PQ给药，Prdx 6-/-小鼠对肺损伤的易感性增加。因此，Prdx 6保护肺免受PQ毒性，如先前对于高氧所示，表明其作为重要的肺抗氧化酶发挥作用。
Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.